Intrinsic neuronal activation of CXCR4 in regulation of regeneration program of the primary sensory neurons



Year of publication 2022
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Description Chemokine signaling was initially recognized to play a role in immune cell trafficking and recirculation with intracellular modulation of cytoskeletal elements. The chemokine CXCL12/CXCR4 axis is involved in a broad spectrum of processes associated with the development, degeneration and regeneration of the nervous system tissue. The experimental models of the rat sciatic nerve injury were used for in vivo and in vitro monitoring of neurite regeneration capacity of the primary sensory neurons prepared from cervical dorsal root ganglia (DRG). We investigated the regulation of CXCL12 and CXCR4 proteins and mRNAs in the cervical and lumbar DRG 7 days after unilateral sciatic nerve compression or transection. Axon regeneration distal to the ulnar nerve (UN) crush was assessed after sciatic nerve lesions and CXCR4 inhibition by AMD3100. Immunohistochemical and RT-PCR analysis revealed increased levels of CXCL12 and CXCR4 proteins and mRNAs bilaterally in both lumbar and cervical DRG after sciatic nerve lesions. The length of SCG10 immunopositive axons distal to UN crush reached a significantly longer distance after sciatic nerve lesions compared with controls. Intrathecal application of AMD3100 reduced protein levels of both CXCR4 and CXCL12 as well as the distance reached by the regenerating axons. The results indicate that intrinsic CXCL12/CXCR4 signaling is involved in the initiation of a pro-regenerative program in the DRG neurons to promote their axon regeneration after nerve injury.
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